Acne vulgaris is a condition that affects nearly 100% of people between the ages of 12 and 17, although some adults continue to suffer from the condition well into their thirties or beyond. Acne lesions are commonly located on the face, but the lesions can also be found on the neck, chest, back, shoulders, scalp, upper arms, and legs. It has been estimated that Americans spend well over one hundred million dollars for the treatment of acne each year.
Acne occurs in response to clogged hair follicles. Initially, sebaceous glands associated with a hair follicle fill the follicle with sebum, an oil-like substance. Dead skin cells lining the hair follicle slough off into the follicle. Normally, the sebum, dead skin cells, and other substances are routinely eliminated from the follicle. When the sebum and dead skin cells form a plug in the follicle, however, a comedone develops. An open comedone occurs when the opening of the follicular canal dilates and the plug protrudes from the canal and turns a characteristic dark color. Open comedones are also referred to as “blackheads” as a result of their characteristic dark color upon exposure to the outside surface of the skin. Closed comedones occur when the follicle is covered, e.g., with a layer of cells, such that the plug does not reach the external environment. Closed comedones are also referred to as “whiteheads” given their characteristic white color.
The production of sebum and dead skin cells lining the follicle increases dramatically during puberty in response to hormonal changes. It is this increased production of these products that causes adolescents to be the most likely individuals to suffer from acne.
Plugs that are not removed from open and closed comedones may swell further. Additional sebum and dead skin cells may accumulate in the clogged follicle. In addition, bacteria such as Propionibacterium acnes may multiply, secreting enzymes that hydrolyze sebum into free fatty acids. The enzymes and the free fatty acids trigger the inflammatory process. As a result, white blood cells such as neutrophils migrate to the follicle, causing an erythematous papule to develop. With continued sebum production and bacterial colonization, the follicle ruptures, causing its contents to spill into the dermis. Continuation of this severe inflammation can cause a cyst.
Based on its etiology, acne may be classified into one of three categories: comedonal, inflammatory, and nodulocystic. Comedonal acne consists predominately of open or closed comedones with little or no accompanying inflammation. Eythromatous papules and pustules characterize inflammatory acne, but comedones may also be present. Nodulocystic acne may consist of comedones and inflammatory lesions, as well as deeper nodules and cysts.
Pharmacotherapy is used to treat acne. Systemic therapy includes oral contraceptives, erythromycin, tetracyclines, doxycycline, minocycline, and isotretinoin. Systemic therapy, however, has many drawbacks. For example, resistance may be developed to antibiotics such as erythromycin, tetracycline, doxycycline, and minocycline. Nishijima et al. (2000) J. Dermatol. 27(5):318-323. Oral contraceptives are inappropriate for male patients as well as for certain populations of female patients, e.g., female patients with a history of breast carcinoma or thromboembolic disorders. Due to its teratogenic activity, isotretinoin therapy requires that female patients not become pregnant during treatment. Furthermore, systemic administration causes systemic side effects, as relatively high levels of the drug must circulate throughout the entire body.
Topical therapy addresses some of the concerns associated with systemic therapy and represents a useful approach to treating individuals suffering from acne. U.S. Pat. No. 5,740,884 describes administering an anti-acne composition containing benzoyl peroxide. U.S. Pat. No. 5,753,637 to Fried describes topical administration of a combination of benzoyl peroxide, salicylic acid, and a vasoconstrictor to treat an individual suffering from acne. U.S. Pat. No. 5,958,984 to Devillez describes topically applying a composition containing hydrogen peroxide.
While topical administration of any one of these compositions may work for some individuals some of time, additional regimens for treating acne and other inflammatory dermatoses are desired. The present invention addresses these and other needs in the art by providing novel methods and formulations for treating inflammatory dermatoses, including sebaceous gland disorders such as acne vulgaris, as will be discussed in detail herein.